Data on safety, effectiveness of common acne drug unreliable, some researchers say

(Reuters Health) – – Isotretinoin, a drug for severe chronic acne, has long been linked to miscarriages, birth defects and other serious problems, but a research review suggests much of data on the drug’s safety, effectiveness and side effects may be unreliable.

The analysis in the Cochrane Database of Systematic Reviews concludes that the available evidence is of such low quality that it’s hard to say for sure how well isotretinoin works or how dangerous it may be.

“After 35 years of use, oral isotretinoin is widely accepted among dermatologists as the most effective available treatment for acne,” said a coauthor of the analysis, Dr. Edileia Bagatin of the Universidade Federal de Sao Paulo in Brazil.

“But lack of high quality evidence observed in this systematic review raises uncertainties regarding its real effectiveness and safety,” Bagatin said by email.

Almost a decade ago, Hoffmann-LaRoche stopped selling its brand-name version of isotretinoin, Accutane, in the wake of lawsuits over side effects and diminishing sales. Generic versions of isotretinoin are still prescribed for severe acne and carry a “black box” warning, the strictest issued by the U.S. Food and Drug Administration, barring use by women who are or may become pregnant, because of the risk of birth defects.

The FDA also warns that isotretinoin may increase the risk for inflammatory bowel disease and psychiatric side effects including depression, psychosis, and suicidal thoughts. But the American Academy of Dermatology maintains that evidence for these risks is inconclusive and still supports use of isotretinoin for severe acne as long as doctors monitor patients for side effects.

More than four in five teens eventually develop acne, Bagatin and colleagues note, usually on the face but sometimes also on the back and chest. Untreated severe acne has been linked to depression and other mental health problems.

For the Cochrane analysis, researchers examined data from 31 previous studies with a total of 3,836 patients. Most were male.

Three studies comparing oral isotretinoin to antibiotics for 20 to 24 weeks found no difference in the reduction of acne, but the researchers felt the evidence was low quality.

Fourteen studies compared different doses of isotretinoin for 12 to 32 weeks and failed to detect serious side effects; again, researchers said the evidence was low quality. Less serious side effects, including dry skin, hair loss, and itching, were assessed in 13 studies but researchers were uncertain whether there were any meaningful differences based on different doses of the drug.

From clinical experience, however, doctors consider isotretinoin the “gold standard” for treating severe acne, said Dr. Felix Boon-Bin Yap of the University Tunku Abdul Rahman and Sunway Medical Centre in Selangor, Malaysia.

“The studies included in this analysis are of low evidence and should be taken with a pinch of salt,” Yap said by email.

Although the Cochrane analysis found isotretinoin might not work better than antibiotics, long-term use of antibiotics can contribute to antibiotic resistance and make these drugs ineffective against infections, Yap, who wasn’t involved in the Cochrane study, said by email.

If anything, the Cochrane review highlights the need for standardized research on acne, said Dr. Megha Tollefson of the Mayo Clinic in Rochester, Minnesota.

Most patients taking isotretinoin have tried antibiotics and other medications without success, Tollefson, who wasn’t involved in the Cochrane study, said by email.

“Isotretinoin is an excellent (both effective and safe) medication for the treatment of acne in the correct setting, and is very appropriate to use in patients including teenagers with moderate to severe acne,” Tollefson said.